Acute and chronic diseases of the lung remain major healthcare problems. Each year nearly 350,000 Americans die of some form of lung disease. Mechanical ventilation provides short-term support for these patients, but longer term support can lead to barotrauma, volutrauma, and other iatrogenic injuries, further exacerbating the respiratory insufficiency. Extracorporeal membrane oxygenation (ECMO) can provide longer term respiratory support but is complex and significantly limits a patient's mobility. This project will develop a compact respiratory assist device, the Paracorporeal Ambulatory Assist Lung (PAAL), to replace ECMO as a bridge to transplant or recovery in patients with acute and chronic lung failure. The PAAL is a fully integrated blood pump and gas exchange module and is designed for peripheral cannulation (e.g. jugular to femoral) or central cannulation (e.g. right atrium to pulmonary artery and worn on a holster or vest. The PAAL will be designed for longer-term respiratory support (1-3 months before change-out) at 70-100% of normal metabolic requirements, while pumping blood from 2 to 3.5 Liters/min. The specific aims of project are 1) To optimize the design and operational parameters of the PAAL to meet requirements for blood pumping, gas exchange, priming volume, and form factor; 2) To build PAAL prototypes along the design development pathway for bench characterization studies; 3) To improve hemocompatibility of the PAAL by exploring novel molecular Zwitterionic coatings; and 4) To perform acute and chronic animal studies in healthy sheep to demonstrate the in-vivo performance and hemocompatibility of the PAAL device and its interaction with the cardiopulmonary system.